Transdermal drug delivery is an area of interest, particularly as an alternative to drug delivery via needle injection. Examples of transdermal drug delivery include the use of transdermal patches to facilitate the diffusion of a drug into the skin.
The stratum corneum provides the most significant barrier to diffusion of a topically applied drug into the body of a patient. The stratum corneum is the top layer of the skin and varies in thickness from approximately ten to several hundred micrometers, depending on the region of the body. It is composed of layers of dead, flattened keratinocytes surrounded by a lipid matrix, which together act as a brick-and-mortar system that is difficult to penetrate.
Most transdermal drug delivery applications utilize at least one of two main pathways by which drugs can cross the skin and reach the systemic circulation. Using the “transcellular pathway” drugs cross the skin by directly passing through both the phospholipids membranes and the cytoplasm of the dead keratinocytes that constitute the stratum corneum. Although this is the path of shortest distance, the drugs encounter significant resistance to permeation. Using the “intercellular pathway” drug passes through the small spaces between the cells of the skin, making the route more tortuous. Although the thickness of the stratum corneum is only about 20 μm, the actual diffusional path of most molecules crossing the skin is on the order of 400 μm. The 20-fold increase in the actual path of permeating molecules greatly reduces the rate of drug penetration.
Another transdermal drug delivery approach utilizes high velocity jets to impart sufficient momentum to a drug form to cause the drug form to breach the stratum corneum. Most commonly high velocity jet injectors are liquid-based. Liquid-based high velocity jet injectors produce liquid jets composed of liquid solutions or colloidal suspensions of drug macromolecules to deliver the drug to the patient. The liquid jet velocity may be in the range of 100 m/s to 150 m/s. The use of liquid-based high velocity injectors has not achieved wide acceptance due to various challenges including: splashing, which risks contamination and results in drug waste; pain and bruising due to lack of control over liquid penetration; high energy requirements; slow delivery rates; usability challenges and operational skill requirements, which militate against the high reproducibility required of a drug delivery device; and formulation challenges caused by jetting constraints such as viscosity and surface tension.
Accordingly, it would be desirable to provide new methods, devices, and systems for delivering drugs to patients.